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Single-cell multi-omics sequencing revealed cytoskeleton defects led to human embryonic arrest characterized with zygotic genome activation

ABSTRACT: Human in vitro-fertilized (IVF) embryos exhibit low developmental capabilities. However, the mechanisms underlying human embryonic arrest remain unclear. Here, using single-cell multi-omics sequencing approach, we simultaneously dissected the alteration of transcriptome, chromatin accessibility and DNA methylome in human early embryos arrested for unexplained reasons. Human arrested embryos displayed transcriptome disorders, including distorted microtubule cytoskeleton, increased genomic instability and impaired glycolysis, which were coordinated with multiple epigenetic reprogramming defects. Moreover, we identified Aurora A kinase (AURKA) repression was a reason for human embryonic arrest. Mechanistically, human arrested embryos from AURKA inhibited group resembled the reprogramming abnormalties of clinically arrested embryos in terms of transcriptome, DNA methylome, chromatin accessibility and H3K4me3. Through mitosis-independent sequential activation of zygotic genome in human arrested embryos, we found YY1 contributed to human major zygotic genome activation (ZGA). Collectively, our study decodes the reprogramming abnormalities and mechanisms for human embryonic arrest and key regulators of human ZGA.

ORGANISM(S): Homo sapiens

PROVIDER: GSE247678 | GEO | 2023/11/17

REPOSITORIES: GEO

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